The anophthalmic mutant mouse provides an animal model for analyzing the effect of total prenatal deafferentation on developing and adult mammalian visual systems. The validity of this model is being defined through light and electron microscopic analysis coupled with the use of tracers to label axoplasmic flow. Current findings indicate considerable similarity between the dorsal lateral geniculate nucleus (dLGN) of anophthalmic and postnatally enucleated mice, except for quantitative differences in the number of neurons and neuroglia. Analysis of the anophthalmic and enucleated mice will be continued to define the connectivity between the dLGN and striate cortex (area 17) as well as between the thalamic lateralis posterior nucleus (LP) and the striate cortex, through the use of horseradish peroxidase, as well as autoradiography. The development of the visual system of the anophthalmic mutant (day 12 gestation to birth) will be compared with that of control mice. This comparison may identify, in the anophthalmic condition, temporal or abnormal disturbances in the differentiation in the visual centers, and whether or not independent abnormalities exist elsewhere in the central nervous system. The ultrastructure of stellate and pyramidal cells of the striate cortex in adult anophthalmic and normal mice will be compared and related to existing physiological findings on the mouse striate cortex. Our ultrastructural analysis of the anophthalmic dLGN demonstrated that the retinal afferents are replaced by distinctive large terminals, which are only partly cortical in origin. To identify their origin more fully, tracers (labelled amino acid and horseradish peroxidase) will be injected into thalamic nuclei and appropriate lesions will be made. Our current work demonstrates an aberrant pathway between the thalamic LP nucleus and the striate cortex in the anophthalmic mutant. To determine whether this connection exists after enucleation, tracers studies via autoradiography (iontophoretic injection of amino acids) as well as injection of horseradish peroxidase to visualize efferent and afferent pathways. The one-eyed Naked Splotch mutant will be used as a system to study prenatal unilateral deafferentation.